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A relatively high molecular weight of 4-arm star PELA was obtained by ring-opening polymerization of L-lactic acid O-carboxyanhydride with 4-arm-PEG in the presence of DMAP as an initiator. The results via1H NMR and 13C NMR show that the end of the star PELA chain is a hydroxyl group and the central core is a PEG group. Rotavirus (strain SA11) was incorporated into 4-arm star PELA microspheres formulated by the water in oil in water emulsification solvent extraction method. The microspheres produced were spherical, and the mean diameter was 1.34 μm with a narrow size distribution. The drug release profile displayed a low burst release effect of 1.8% on the first day and a sustained release of antigen over 100 days. After the immunization of mice, the microsphere-entrapped RV elicited improved and long-lasting IgA and IgG antibody response in serum detected by ELISA in comparison to the free RV antigen. This study shows that 4-arm-PEG is an effective initiator for the ring-opening polymerization of Lac-OCA by DMAP as an initiator and that the resulting polymer is useful as a delivery system for the rotavirus vaccine.